Optic Nerve Sheath Meningioma
Optic Nerve Sheath Meningiomas (ONSM) are uncommon, benign neoplasms originating from the meningothelial cells of the meninges surrounding the optic nerve. The tumor may arise from either the intraorbital or intracanalicular portions of the optic nerve where there is a meningeal sheath. Primary ONSM should be differentiated from secondary intracranial meningiomas that extend anteriorly to involve the optic nerve. Although considered benign tumors, primary ONSMs cause slow, progressive vision loss secondary to compression of the adjacent optic nerve and its blood supply. This monograph discusses primary ONSM.
Epidemiology and Risk Factors
Although rare, ONSM is the second-most common primary optic nerve tumor and represents 1-2% of all meningioma.. They account for one-third of primary optic nerve tumors. The incidence of ONSM is highest in adult women in the fourth or fifth decades of life, with women being three times more likely than men to be affected. ONSM however can rarely occur in children: a review of cases by Dutton showed that only 4% of tumors occurred in patients younger than 20 years.
The etiology of ONSM has not been clearly identified and most are idiopathic. Exposure to ionizing radiation has been associated with meningiomas. ONSM have also been associated with neurofibromatosis type 2. The most common cytogenetic abnormality found in meningiomas is the loss of the long arm of chromosome 22, including the region containing the NF2 gene.
ONSMs consist of proliferations of meningothelial cells which are thought to originate from the arachnoid villi of the arachnoid mater. Grossly, they appear as rounded masses compressing adjacent tissues with well-defined borders. Typically ONSMs grow circumferentially around the optic nerve without invasion of the nerve tissues. They may spread along the length of the nerve and have potential to enter the intracranial space, in which case involvement of the contralateral visual pathway becomes a concern. Histologically, ONSM may have one of several appearances, including syncytial, fibroblastic, transitional, psammomatous (exhibiting psammoma bodies), secretory, or microcystic. These patterns do not convey prognostic information, however. ONSMs may rarely show malignant, invasive characteristics along with a higher rate of recurrence.
Patients with ONSM may be asymptomatic. Symptomatic patients with ONSM most often present with gradually progressive, painless monocular vision loss. Visual acuity at presentation can vary considerably (20/20 to no light perception) due to variable levels of awareness of visual loss. Dutton's review found that 24% of patients had visual acuity of counting fingers or worse, while 45% of patients had visual acuity of 20/40 or better. Evidence of optic nerve dysfunction (e.g., reduced color vision, visual field loss, an ipsilateral relative afferent pupillary defect, and optic atrophy/optic disc edema) are typically present. Patients may demonstrate a classic clinical triad of ONSM: 1) painless, slowly progressive vision loss, 2) optic atrophy, and 3) so called “optociliary shunt vessels." The full triad however is seen in only a minority of cases, however. “Optociliary shunt vessels” are collateral vessels formed in response to chronic occlusion of the central retinal vein (and not a true shunt) and serve to carry blood from the retinal venous circulation to the choroidal circulation (i.e., retinochoroidal venous collateral). These retinochoroidal venous collaterals (RCVC) however are not specific for ONSM. In addition, RCVC are seen in only 30% of patients with ONSM. Patients with orbital ONSM may also have proptosis or extraocular motility deficits, depending on the location and size of the tumor. Funduscopic exam may reveal an initially normal or swollen optic disc, but eventually optic atrophy develops (with or without RCVC).
The diagnosis of ONSM is clinical and then confirmed with neuroimaging. Although computed tomography (CT) of the head and orbit may show the lesion (especially if calcified), magnetic resonance imaging (MRI) of the head and orbit with gadolinium and fat suppression sequences is generally recommended for ONSM. The CT scan findings include diffuse, tubular, lesions with contrast-enhancement. Calcifications may be present within the tumor as well and are better seen on CT. MRI studies of the head and orbit with gadolinium contrast as well as fat suppression sequences are useful for identifying the involvement of the sheath and the radiographic features are usually so typical for ONSM that a biopsy may not be necessary in the appropriate clinical setting. MRI may demonstrate diffuse, tubular thickening of the optic nerve sheath encasing the optic nerve, often producing a characteristic "tram track" sign on axial cuts or a "doughnut" sign on coronal cuts. The tumor usually enhances homogenously and vigorously after contrast infusion. MRI may also be useful in delineating the extent of the tumor and for evaluating for intracranial extension. Ga-68 PET/CT has recently been considered as a diagnostic tool for the detection of meningiomas via exploitation of their somatostatin receptor ligands. Sensitivity and selectivity was found to be 10% higher in the detection of primary or recurrent meningiomas compared to MRI and has also shown high potential in its ability to predict tumor growth rate. PET scan is usually not necessary for the diagnosis of typical ONSM, however. Biopsy of the tumor is not necessary for diagnosis in typical clinical cases with characteristic radiographic features for ONSM and surgery carries a high risk of damage to the optic nerve.
Optic Nerve Glioma, Metastatic disease, Leukemic infiltration, Neurosarcoidosis, Tuberculosis, Gummatous syphilis, Optic Perineuritis, Myelin Oligodendrocytic Glycoprotein (MOG)
Patients with ONSM may be observed if asymptomatic and generally the clinical course and imaging are sufficient to make the diagnosis. Although the lesions are typically histologically benign, symptomatic patients could be offered treatment. The optimal timing of treatment for ONSM is unclear due to the difficulty in predicting the variable natural course of an individual tumor. One case series found a high degree of variability of the change in visual acuity from baseline for 16 patients diagnosed with ONSM whom were then followed expectantly for an average of 6.2 years There were additionally no clear variables identified which could help predict the patients' visual outcomes other than an already poor initial visual acuity.
Historically, management options have included observation, surgical excision, or radiation therapy. A retrospective study by Turbin et al compared visual acuity outcomes in patients who underwent observation, surgical therapy, radiation therapy, or a combination of surgery and radiation. The groups of patients all had statistically similar initial visual acuities. At the end of the follow-up period, however, only the patients who received fractionated external beam radiation treatment alone had visual acuity levels which were not significantly decreased. Likewise, Ratnayake et al demonstrated stereotactic radiotherapy as an excellent option with good relative long-term local control. The MRI based tumor control rate was 100% at 68 months. Also, a more recent retrospective analysis from 2019, which focused on intensity-modulated radiotherapy, showcased an either stable or improved visual acuity rate of 81%. The study elucidated that this technique is suitable for visual stabilization even in patients with a severe deficiency before treatment. Moreover, many previous studies, which focused on fractionated stereotactic radiation therapy, demonstrated either stable or improved visual field rate of 83.3%-100%.  These studies, among others, have suggested that radiation therapy may be considered for ONSM once the decision has been made to intervene and preventing further visual loss is typically the goal. Fractionated stereotactic, intensity-modulated, and 3D conformal radiation therapy is generally considered the preferred therapy for symptomatic ONSM. Stereotactic radiotherapy is well suited for smaller and more well-circumscribed lesions. Adverse effects however include radiation-induced complications such as secondary radiation retinopathy and optic neuropathy, iritis, cataract and hypopituitarism.
Proton therapy is another potential option for the treatment of ONSM. However, research in the use of proton therapy for ONSM is limited. Proton therapy has the potential to reduce late toxicities due to its ability to ensure low scattering doses, a beneficial quality for the management of meningiomas located near the pituitary gland.
Surgical intervention is generally not favored for eyes with useful vision due to the risk of post-operative blindness. Surgery may worsen the vision because of the common pial blood supply shared by the optic nerve and the ONSM. However, surgical excision could be considered in cases in blind eyes with severe proptosis or cosmetic deformity or if there is threat of intracranial spread although this event in clinical practice is rare. A recent case report noted complete resolution of visual symptoms and total tumor resection following surgical resection of ONSM using an endoscopic endonasal approach; some ONSM have morphologies (e.g., exophytic from the optic nerve sheath) that may be amenable to resection on a case by case basis. The authors consider that advancements in neuroimaging and the ability to target every segment of the optic nerve with this technique perhaps makes it a new possibility in the management of selected tumors. Palliative surgery could additionally be considered when there is advanced vision loss along with disfiguring proptosis.
Pediatric ONSM has been shown to have increased malignant potential relative to adult ONSM. Due to a higher rate of intracranial spread, an increased rate of complications following radiotherapy, and a lack of literature concerning radiotherapy in the pediatric population studies suggest that surgical prevention be the primary treatment for children with ONSM. It has also been shown that pediatric ONSM. had greater association with Neurofibromatosis type 2 (NF2) than adults, with some cases reporting up to 35% afflicted children presenting with the genetic disorder.
The natural history of ONSM is typically that of slowly progressive, ipsilateral vision loss. As noted, above, however, the individual rate or progression is quite variable. Nevertheless, an increased likelihood of positive visual outcome post-radiation treatment has been linked to good pre-treatment visual acuity. The mortality rate from ONSM is minimal and therefore any decision for treatment (including stereotactic radiotherapy) must include discussion of the risks and benefits. In general, and at our institution, intensity modulated, 3-dimensional conformal stereotactic radiotherapy is the treatment of choice for symptomatic ONSM.
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